scholarly journals A New Bioink For Improved 3D Bioprinting Of Bone-Like Constructs

2021 ◽  
Author(s):  
Adam Marsh ◽  
Ehsanul Hoque Apu ◽  
Marcus Bunn ◽  
Christopher H Contag ◽  
Nureddin Ashammakhi ◽  
...  

Bone tissue loss can occur due to disease, trauma or following surgery, in each case treatment involving the use of bone grafts or biomaterials is usually required. Recent development of three-dimensional (3D) bioprinting (3DBP) has enabled the printing of customized bone substitutes. Bioinks used for bone 3DBP employ various particulate phases such as ceramic and bioactive glass particles embedded in the bioink creating a composite. When composite bioinks are used for 3DBP based on extrusion, particles are heterogeneously distributed causing damage to cells due to stresses created during flow in the matrix of the composite. Therefore, the objective of this study was to develop cell-friendly osteopromotive bioink mitigating the risk of cell damage due to the flow of particles. Towards this end, we have linked organic and inorganic components, gelatin methacryloyl (GelMA) and Ag-doped bioactive glass (Ag-BaG), to produce a hybrid material, GelMA-Ag-BaG (GAB). The distribution of the elements present in the Ag-BaG in the resulting hybrid GAB structure was examined. Rheological properties of the resulting hydrogel and its printability, as well as the degree of swelling and degradation over time, were also evaluated. GAB was compared to GelMA alone and GelMA-Ag-BaG nanocomposites. Results showed the superiority of the hybrid GAB bioink in terms of homogenous distribution of the elements in the structure, rheological properties, printability, and degradation profiles. Accordingly, this new bioink represents a major advance for bone 3DBP.

2019 ◽  
Vol 5 (2.2) ◽  
pp. 3 ◽  
Author(s):  
Krishna C. R. Kolan ◽  
Julie A. Semon ◽  
Bradley Bromet ◽  
Delbert E. Day ◽  
Ming C. Leu

Three-dimensional (3D) bioprinting technologies have shown great potential in the fabrication of 3D models for different human tissues. Stem cells are an attractive cell source in tissue engineering as they can be directed by material and environmental cues to differentiate into multiple cell types for tissue repair and regeneration. In this study, we investigate the viability of human adipose-derived mesenchymal stem cells (ASCs) in alginate-gelatin (Alg-Gel) hydrogel bioprinted with or without bioactive glass. Highly angiogenic borate bioactive glass (13-93B3) in 50 wt% is added to polycaprolactone (PCL) to fabricate scaffolds using a solvent-based extrusion 3D bioprinting technique. The fabricated scaffolds with 12 × 12 × 1 mm3 in overall dimensions are physically characterized, and the glass dissolution from PCL/glass composite over a period of 28 days is studied. Alg-Gel composite hydrogel is used as a bioink to suspend ASCs, and scaffolds are then bioprinted in different configurations: Bioink only, PCL+bioink, and PCL/glass+bioink, to investigate ASC viability. The results indicate the feasibility of the solvent-based bioprinting process to fabricate 3D cellularized scaffolds with more than 80% viability on day 0. The decrease in viability after 7 days due to glass concentration and static culture conditions is discussed. The feasibility of modifying Alg-Gel with 13-93B3 glass for bioprinting is also investigated, and the results are discussed.


Author(s):  
Cartwright Nelson ◽  
Slesha Tuladhar ◽  
Md Ahasan Habib

Abstract Three-dimensional bioprinting is a rapidly growing field attempting to recreate functional tissues for medical and pharmaceutical purposes. Development of functional tissue requires deposition of multiple biomaterials encapsulating multiple cell types i.e. bio-ink necessitating switching ability between bio-inks. Existing systems use more than one print head to achieve this complex interchangeable deposition, which decreases efficiency, structural integrity, and accuracy. In this research, we developed a nozzle system capable of switching between multiple bio-inks with continuous deposition ensuring the minimum transition distance so that precise deposition transitioning can be achieved. Finally, the effect of rheological properties of different bio-material compositions on the transition distance is investigated by fabricating the sample scaffolds.


2020 ◽  
Vol 21 (19) ◽  
pp. 7012 ◽  
Author(s):  
Tullio Genova ◽  
Ilaria Roato ◽  
Massimo Carossa ◽  
Chiara Motta ◽  
Davide Cavagnetto ◽  
...  

Reconstruction of bony defects is challenging when conventional grafting methods are used because of their intrinsic limitations (biological cost and/or biological properties). Bone regeneration techniques are rapidly evolving since the introduction of three-dimensional (3D) bioprinting. Bone tissue engineering is a branch of regenerative medicine that aims to find new solutions to treat bone defects, which can be repaired by 3D printed living tissues. Its aim is to overcome the limitations of conventional treatment options by improving osteoinduction and osteoconduction. Several techniques of bone bioprinting have been developed: inkjet, extrusion, and light-based 3D printers are nowadays available. Bioinks, i.e., the printing materials, also presented an evolution over the years. It seems that these new technologies might be extremely promising for bone regeneration. The purpose of the present review is to give a comprehensive summary of the past, the present, and future developments of bone bioprinting and bioinks, focusing the attention on crucial aspects of bone bioprinting such as selecting cell sources and attaining a viable vascularization within the newly printed bone. The main bioprinters currently available on the market and their characteristics have been taken into consideration, as well.


Author(s):  
Caroline Murphy ◽  
Krishna Kolan ◽  
Wenbin Li ◽  
Julie Semon ◽  
Delbert Day ◽  
...  

 A major limitation of using synthetic scaffolds in tissue engineering applications is insufficient angiogenesis in scaffold interior. Bioactive borate glasses have been shown to promote angiogenesis. There is a need to investigate the biofabrication of polymer composites by incorporating borate glass to increase the angiogenic capacity of the fabricated scaffolds. In this study, we investigated the bioprinting of human adipose stem cells (ASCs) with a polycaprolactone (PCL)/bioactive borate glass composite. Borate glass at the concentration of 10 to 50 weight %, was added to a mixture of PCL and organic solvent to make an extrudable paste. ASCs suspended in Matrigel were ejected as droplets using a second syringe. Scaffolds measuring 10x10x1 mm3 in overall dimensions with pore sizes ranging from 100 – 300 µm were fabricated. Degradation of the scaffolds in cell culture medium showed a controlled release of bioactive glass for up to two weeks. The viability of ASCs printed on the scaffold was investigated during the same time period. This 3D bioprinting method shows a high potential to create a bioactive, highly angiogenic three-dimensional environment required for complex and dynamic interactions that govern the cell’s behavior in vivo.


Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2795
Author(s):  
Elisa Fiume ◽  
Sara Ciavattini ◽  
Enrica Verné ◽  
Francesco Baino

Since 2006, the foam replica method has been commonly recognized as a valuable technology for the production of highly porous bioactive glass scaffolds showing three-dimensional, open-cell structures closely mimicking that of natural trabecular bone. Despite this, there are important drawbacks making the usage of foam-replicated glass scaffolds a difficult achievement in clinical practice; among these, certainly the high operator-dependency of the overall manufacturing process is one of the most crucial, limiting the scalability to industrial production and, thus, the spread of foam-replicated synthetic bone substitutes for effective use in routine management of bone defect. The present review opens a window on the versatile world of the foam replica technique, focusing the dissertation on scaffold properties analyzed in relation to various processing parameters, in order to better understand which are the real issues behind the bottleneck that still puts this technology on the Olympus of the most used techniques in laboratory practice, without moving, unfortunately, to a more concrete application. Specifically, scaffold morphology, mechanical and mass transport properties will be reviewed in detail, considering the various templates proposed till now by several research groups all over the world. In the end, a comprehensive overview of in vivo studies on bioactive glass foams will be provided, in order to put an emphasis on scaffold performances in a complex three-dimensional environment.


2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.


2018 ◽  
Vol 69 (2) ◽  
pp. 429-433
Author(s):  
Solyom Arpad ◽  
Cristian Trambitas ◽  
Ecaterina Matei ◽  
Eugeniu Vasile ◽  
Fodor Pal ◽  
...  

Osteoplasty, is a procedure mostly applied in complicated bone fractures. Nowadays this method is widely used in primary fracture treatment while the native bone graft is progressively replaced with various synthetic bone substitutes. From the numerous bone grafts we�d like to mention a representative of ceramics, the S53P4 bioactive glass. (BonAlive�). The aim of this study was to investigate the healing process of different fracture types generated on rabbit femurs. During this experiment we used seven common European rabbits. We separated these animals into two groups; in the first group we surgically generated a total fracture in the middle 1/3 of the femur, while in the second group, we produced only a bone defect on the femur. The osteoplasty was carried out with bioactive glass and autologous bone grafts. The radiographic follow-up was immediate after the operation and after 3, 6 and 7 weeks. The animals were euthanized after 19, 20 and 21 weeks, for histomorphometric examination of the femur. It was also studied the ionic release from the used bioactive glass at physiological pH and the etching of the glass was studied by Scanning Electron Microscopy.


2012 ◽  
Vol 9 (1) ◽  
pp. 142-146
Author(s):  
O.A. Solnyshkina

In this work the 3D dynamics of two immiscible liquids in unbounded domain at low Reynolds numbers is considered. The numerical method is based on the boundary element method, which is very efficient for simulation of the three-dimensional problems in infinite domains. To accelerate calculations and increase the problem size, a heterogeneous approach to parallelization of the computations on the central (CPU) and graphics (GPU) processors is applied. To accelerate the iterative solver (GMRES) and overcome the limitations associated with the size of the memory of the computation system, the software component of the matrix-vector product


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1629
Author(s):  
Colin H. Quinn ◽  
Andee M. Beierle ◽  
Elizabeth A. Beierle

In the quest to advance neuroblastoma therapeutics, there is a need to have a deeper understanding of the tumor microenvironment (TME). From extracellular matrix proteins to tumor associated macrophages, the TME is a robust and diverse network functioning in symbiosis with the solid tumor. Herein, we review the major components of the TME including the extracellular matrix, cytokines, immune cells, and vasculature that support a more aggressive neuroblastoma phenotype and encumber current therapeutic interventions. Contemporary treatments for neuroblastoma are the result of traditional two-dimensional culture studies and in vivo models that have been translated to clinical trials. These pre-clinical studies are costly, time consuming, and neglect the study of cofounding factors such as the contributions of the TME. Three-dimensional (3D) bioprinting has become a novel approach to studying adult cancers and is just now incorporating portions of the TME and advancing to study pediatric solid. We review the methods of 3D bioprinting, how researchers have included TME pieces into the prints, and highlight present studies using neuroblastoma. Ultimately, incorporating the elements of the TME that affect neuroblastoma responses to therapy will improve the development of innovative and novel treatments. The use of 3D bioprinting to achieve this aim will prove useful in developing optimal therapies for children with neuroblastoma.


Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 946
Author(s):  
Katharina Kowalewicz ◽  
Elke Vorndran ◽  
Franziska Feichtner ◽  
Anja-Christina Waselau ◽  
Manuel Brueckner ◽  
...  

Calcium magnesium phosphate cements (CMPCs) are promising bone substitutes and experience great interest in research. Therefore, in-vivo degradation behavior, osseointegration and biocompatibility of three-dimensional (3D) powder-printed CMPC scaffolds were investigated in the present study. The materials Mg225 (Ca0.75Mg2.25(PO4)2) and Mg225d (Mg225 treated with diammonium hydrogen phosphate (DAHP)) were implanted as cylindrical scaffolds (h = 5 mm, Ø = 3.8 mm) in both lateral femoral condyles in rabbits and compared with tricalcium phosphate (TCP). Treatment with DAHP results in the precipitation of struvite, thus reducing pore size and overall porosity and increasing pressure stability. Over 6 weeks, the scaffolds were evaluated clinically, radiologically, with Micro-Computed Tomography (µCT) and histological examinations. All scaffolds showed excellent biocompatibility. X-ray and in-vivo µCT examinations showed a volume decrease and increasing osseointegration over time. Structure loss and volume decrease were most evident in Mg225. Histologically, all scaffolds degraded centripetally and were completely traversed by new bone, in which the remaining scaffold material was embedded. While after 6 weeks, Mg225d and TCP were still visible as a network, only individual particles of Mg225 were present. Based on these results, Mg225 and Mg225d appear to be promising bone substitutes for various loading situations that should be investigated further.


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